[34] Grass- Kapanke et al., 2011

300 (G = 149; P = 147) subjects with very mild cognitive impairment (vMCI) reported spontaneously or upon inquiry;

MMSE 27.8 ± 1.5

WMS III Faces I+II 33.9 ± 5.7

WTS-DT 308.5 ± 44.8

Perceived cognitive impairment present for at least 3 months with widely preserved general cognitive function, MMSE ≥ 23, No indication of dementia

Intact activities of daily living by inquiry

(subtle difficulties are acceptable)

At least one SD worse than mean of normative group in at least one cognitive test (WMS III Faces I+II, WTA-ALS, WTS-DT, TT)

Multicenter, randomized double blind parallel group placebo controlled

(exploratory)

range 45 to 65 years

Mean age in ginkgo group 55.3 ± 5.7 years

EGb 761 at 240 mg/day for a period of 12 weeks

Primary goal: assess treatment effects and tolerability of GBE in subjects below the age of retirement with very mild cognitive impairment (vMCI), also named mild mental impairment, MMI

1) Wechsler Memory Scale III—Faces I and II (WMS III Faces I+II),

2) Vienna Test System Work Performance Series (Arbeitsleistungsserie, WTS-ALS)

3) Vienna Test System Determination Test (WTS-DT)

4) Appointments Test (Termine Test, TT)

5) Mental Balance Scale (Befindlichkeitsskala, BfS’)

6) SF-36 Health Survey

1) GBE showed better immediate recognition (WMSIII-Faces I; p = 0.04) and delayed recognition (WMSM III-Faces II; p = 0.27), but significant superiority was seen in subgroup of more impaired subjects (WMS III-Faces I and WMS III-Faces II, p = 0.02 and p = 0.01 respectively). Thus, there is a trend in favor of EGb in memory.

2) Significant improvements in concentration and fatigability (WTS-ALS; p = 0.01)

3) No significant improvement in attention (WTS-DT; p = 0.21)

4) Significant improvement in memory, free and delay recall (TT immediate recall p = 0.06 and TT delayed recall p = 0.03) for the more distinctly impaired subjects

5) No effect in mental balance (BfS’; p = 0.92)

6) Significant improvement in perceived physical health (SF36; p = 0.04) but not in mental health (p = 0.15)

As an overall, cognitive effects were more pronounced and more consistent (p < 0.025 in 4 of 5 tests) in subjects with lower memory function at baseline

[35] Brautigam et al., 1998

241 (G = 77 (HD); 82 (LD); P = 82) non-institutionalized elderly individuals with self-reported memory complaints

Mean MMSE 26.30 ± 2.31 for HD and 26.01 ± 2.54 for LD

Self-reported memory and/or concentration complaints

MMSE≥20

Beck Depression Inventory score<21

Multicenter, randomized double blind placebo controlled

range 55-86 years

Mean age in ginkgo group 68.9 ± 7.8 years

Geriaforce (alcohol/water extract 3 times/day for 24 weeks

High dose (HD):40 drops (1.9 ml) undiluted ginkgo extract

Low dose (LD):40 drops (1.9 ml) (ginkgo extract 1:1 with placebo)

Primary goal: efficacy and tolerance of two dosages of an alcohol/water extract of ginkgo biloba

Psychometric test battery:

1) Expanded Mental Control Test (EMCT) (measuring attention and concentration)

2) Benton Test of Visual Retention-Revised (measures short term visual memory),

3) Rey Test part 1 (measures short-term memory and learning curve)

4) Rey Test part 2 (measures long term memory: recognition)

5) Beck depression inventory

6) Contrast analysis between treatments

7) Side effects

Subjective tests:

8) Subjective perception of memory and concentration (Likert scale)

1) No significant improvement in attention and concentration (EMCT; p = 0.935)

2) Significant improvement of short-term visual memory (Benton test with contrast analysis; p = 0.0076)

3) No significant improvement short-term memory and learning curve (Rey Test part 1 (p = 0.652)

4) No significant improvement in long term memory recognition (Rey Test part 2 (p = 0.246)

5) No significant differences in improvement perception of memory and concentration (p = 0.258) and for severity of memory complaints, judged by the physicians (p = 0.988).

6) Significant differences between the groups: PL < HD < LD (p = 0.0076), which suggests that LD (low dose) is the optimal dose.

7) Most frequent side effects were gastrointestinal complaints

8) No relation was found between treatment groups and efficacy and tolerability

[36] Allain et al., 1993

18 (G1 = 18; G2 = 18; P = 18; cross over study)

elderly subjects with slightly age-related memory impairment

MMSE 27.2 ± 0.9

Non-dement

MMSE range 25 to 28

Cognitive impairment reflected objectively by a difference of more than 1 SD in comparison with a group of young subjects on an inclusion memory test (immediate recall of three lists of words)

Single center, cross over, randomized, double blind, placebo controlled

range 60 to 80 yeas

Mean age in ginkgo group 69.3 ± 1.2 years

EGb 761 at a daily dose of 320 mg or 600 mg over 3 weeks

(Psychometric testing started 1 h after administration)

Primary goal: efficacy

Psychometric battery (dual-coding test, words and drawings in relation to variable presentation times)

1) Number of correct recalls of words and drawings

2) Differences in the number of drawings and words recalled correctly (D/W)

3) Presentation time at which a break was observed on the curves

1) No significant differences between the treatments on word recall and drawings

2)No significant differences on D/W differences

3)Significant shift (p < 0.05) towards a shorter presentation time between ginkgo and placebo (break point at 480 ms and dual coding at 960 ms VS break point 960 ms and dual coding beginning at 1920 ms. respectively), thus, there is an improvement in the speed of information processing